Liver Tumour Ablation: Alcohol, RFA, Microwave and Cryo

Liver tumour ablation destroys a tumour through a needle placed under ultrasound or CT guidance, either by injecting a chemical (alcohol) or by delivering energy: heat from radiofrequency or microwave, cold from cryoablation, or electrical pulses from irreversible electroporation. Each technique has a defined place, and the choice depends on the tumour's size, its position and the vessels and organs around it.

Dr. Shobhit Singh, Consultant - Intervention Radiologist - Gastroenterology & Hepatology, BLK-Max Super Speciality Hospital, New Delhi, India, set out how each method works, where it fails and how his team protects neighbouring structures, illustrated with clinical cases. For how ablation fits into liver cancer staging and transplant planning, see the complete guide to hepatobiliary interventional radiology.

Where ablation fits in liver cancer treatment

Ablation is a first-line option for very early and early hepatocellular carcinoma (HCC): one or a few small tumours in a patient whose liver function allows treatment. In Dr. Singh's words, ablation can give a complete cure many times. It also serves as a bridge to transplant, holding the tumour in check while a donor and finances are arranged.

Percutaneous ablation falls into two groups:

• Chemical ablation: alcohol injected directly into the tumour.
• Energy-based ablation: radiofrequency, microwave, cryoablation, irreversible electroporation (IRE) and histotripsy, each of which directs energy into the tumour to kill its cells.

The aim in every case is the same: necrosis (death) of all tumour cells, with a margin of safety and as little injury as possible to the rest of the liver.

Alcohol (chemical) ablation

Alcohol ablation is a basic, low-cost option. It works because of a mechanical contrast inside a cirrhotic liver. An HCC nodule is soft, while the cirrhotic liver around it is firm. Alcohol injected into the soft tumour diffuses through it easily and tends not to escape, so it stays contained and kills the tumour.

Inside the tumour, the alcohol denatures proteins, dehydrates cells and thromboses small vessels, and the tissue becomes necrotic.

The procedure

1. Under sedation or local anaesthesia, a fine spinal needle of 20 to 22 gauge is inserted into the liver under ultrasound guidance (CT guidance is also possible).
2. The needle is passed through the tumour to its far edge.
3. It is then withdrawn slowly while alcohol is injected, so that the whole tumour is covered. On ultrasound the injected fluid shows as a bright area; once it covers the tumour, the injection stops and the needle is removed.

It is a day-care procedure taking 10 to 15 minutes. In one case Dr. Singh showed, a small tumour in segment 7 was treated this way, and contrast CT at around six to eight weeks showed no enhancement within the lesion: the tumour was necrotic.

Limits

Alcohol ablation suits tumours under 1 to 2 cm. Several sessions may be needed, and the direction in which the alcohol spreads cannot be controlled. If it leaks into normal liver, it can cause severe pain.

Asked about that risk of collateral damage, Dr. Singh said there is always a chance of the injected alcohol spilling into the normal liver, which is why the technique is not offered to every patient. He uses it mainly for lesions under 1 cm that have a capsule, because a well-defined, encapsulated HCC keeps the alcohol inside. Even so, there have been cases where it escaped into the normal liver and caused pain. For that reason microwave ablation has largely taken over: for a lesion of about 2 cm, his team would now perform a single thermal ablation rather than several sessions of alcohol injection.

Radiofrequency ablation (RFA)

Radiofrequency ablation passes a high-frequency alternating current from a generator through a needle into the tumour. The current agitates the ions in the tumour tissue, and the resulting frictional heat causes necrosis. A grounding pad on the patient's skin completes the electrical circuit back to the generator.

Probes with several expandable tines (pins) cover a larger area. Dr. Singh described using such probes for tumours larger than 3 cm. Radiofrequency ablation achieves its most reliable complete ablation in tumours up to about 3 cm; beyond that size, the risk of incomplete treatment and local recurrence rises.

Why RFA struggles with large tumours

Above about 5 cm, two problems appear.

• Charring limits heat spread. The ablation must cover the whole tumour plus a margin of about half a centimetre of normal tissue. As tissue burns and chars, it resists the further passage of heat to adjacent tumour cells, so heat propagation falls over time.
• The heat-sink effect. If a blood vessel lies next to the tumour, the flowing blood carries the heat away. Part of the tumour does not burn completely, and residual tumour remains.

Newer-generation devices address this with expandable tines, clustered electrodes and internally cooled electrodes, which deliver more heat.

For a large tumour, the needle is placed in several directions in turn: one zone is burned, the needle is repositioned and the next zone is burned, to achieve homogeneous coverage. In one of Dr. Singh's cases, a large enhancing tumour treated under ultrasound and sedation showed no enhancing area on contrast CT at two months: the tumour was completely burned out.

Microwave ablation

Microwave ablation is the technique now gaining most ground after RFA, and Dr. Singh's team also uses it. The procedure looks the same: a needle (antenna) is placed in the tumour and connected to a generator. The generator produces an electromagnetic field that makes water molecules rotate rapidly and homogeneously, and the tumour is destroyed by the resulting heat. Cold saline circulates inside the antenna so that it does not overheat.

Microwave vs radiofrequency ablation: why microwave often performs better

• Faster, larger ablation zones. Heating is active and does not rely on conduction through tissue.
• Less heat-sink effect. A tumour next to a blood vessel is still burned, and the vessel itself is less likely to be injured.
• No grounding pads. The risk of skin burns at pad sites is removed.

Newer antennas use carbon dioxide cooling, reach power of 140 to 150 watts and produce spherical ablation zones, which make it easier to target a tumour and achieve a large ablation zone.

Cases

In one patient, contrast MRI showed an enhancing tumour lying very close to the portal vein. Microwave ablation was performed under ultrasound guidance. At two months there was no active enhancing area, later scans showed the treated area shrinking, and the portal vein remained patent, with no narrowing or injury. In another, a large tumour in segment 8 was ablated under CT guidance, and the two-month scan showed a burnt-out ablation zone with no residual tumour.

Cryoablation

Cryoablation kills tumour tissue by cold rather than heat. A needle connected to a cryoablation generator is placed in the tumour. Alternating cycles of freezing and thawing cool the tissue until an ice ball forms, and the tissue breaks down through direct cellular and vascular injury. Most systems freeze with expanding argon gas and use helium for the active thaw.

Dr. Singh highlighted four advantages:

• It is easy to monitor. The ice ball is clearly visible during treatment, so the extent of ablation can be watched as it happens.
• It is a less painful procedure.
• It can treat larger tumours, because a larger area can be ablated.
• It spares adjacent structures. It does not injure blood vessels or the gallbladder lying next to the tumour.

Cases

In one patient, contrast MRI showed an enhancing tumour very close to the diaphragm. Under CT guidance a cryoablation needle was placed, the ice ball covered the tumour, and delayed imaging showed no residual activity. In a published example he presented, a PET-avid tumour showed no metabolic activity after cryoablation and shrank over the following months, indicating that the tumour had been killed.

Irreversible electroporation (IRE)

Irreversible electroporation is a non-thermal technique. Several needles are placed in the tumour, and very short pulses of high voltage and low energy are delivered between them. The pulses punch multiple holes in the tumour cell membranes, and the cells die. Because tissue temperature does not rise, injury to adjacent structures is minimal.

Dr. Singh was candid about the drawbacks:

• A very steep learning curve. Good results take time to achieve.
• Longer procedures. Microwave, radiofrequency and cryoablation generally use a single needle; IRE needs several.
• Risk of tumour seeding. The needle tract cannot be ablated on withdrawal, so tumour cells may be seeded along it.
• Neuromuscular blockade. An anaesthetist must give a muscle relaxant, otherwise muscle twitching or nerve injury can occur.

IRE is available at very few centres, and his department does not currently offer it.

Histotripsy

Histotripsy uses focused ultrasound pulses aimed at the tumour to cause cavitation (the formation and collapse of microbubbles) within the tumour cells, which breaks them apart. No needle is placed: the patient is positioned much as for a CT or MRI scan, and the energy is focused onto the tumour from outside. Histotripsy is available in very few centres and is not offered in Dr. Singh's department; he presented it to illustrate where the field is heading.

Protecting nearby organs during ablation

Heat does not stop at the tumour's edge. When a tumour lies against the bowel, the diaphragm or another sensitive structure, thermal energy can injure it. Two techniques reduce that risk and improve accuracy.

Hydrodissection. A catheter is placed between the tumour and the adjacent structure and dextrose is injected. The fluid acts as a cushion that absorbs the heat and prevents it from reaching the neighbouring organ.

Contrast-enhanced ultrasound (CEUS). Some tumours are hard to see on standard ultrasound. After an ultrasound contrast agent is injected, a hepatocellular carcinoma typically enhances brightly in the arterial phase and then washes out, appearing darker than the surrounding liver in the later phases. The tumour then becomes visible enough to place the needle precisely before ablation.

Choosing a liver tumour ablation technique

Drawing the session together, the practical choice runs as follows:

Where one lesion cannot be fully treated by ablation alone, for example because a large vessel causes a heat sink, ablation can be combined with transarterial therapy. That approach, and the transarterial techniques themselves, are covered in TACE and TARE for liver cancer. The audience's questions on ablation, including the risk of alcohol leaking into normal liver, are answered on the live discussion page, and specialists who perform these procedures are listed under interventional radiology.